Hartley Jane L, Brown Rachel M, Tybulewicz Aniela, Hayes Peter, Wilson David C, Gillett Peter, McKiernan Patrick
Birmingham Children's Hospital, UK.
J Pediatr Gastroenterol Nutr. 2006 Aug;43(2):217-21. doi: 10.1097/01.mpg.0000228121.44606.9f.
Hyaluronic acid (HA) is removed by the liver via sinusoidal cell adhesion molecules. This is impeded in fibrosis, leading to a rise in serum HA. As a noninvasive marker of fibrosis, HA may obviate the need for liver biopsy.
To evaluate HA as a marker of hepatic fibrosis, in unselected children undergoing liver biopsy.
Ninety-three unselected consecutive children (median age, 7.5 years; range, 0.07-19 years) undergoing a liver biopsy between April 2003 and March 2004 were prospectively recruited. Liver biopsy and fasting HA levels were taken simultaneously. The Ishak score was used to stage fibrosis. Scores of 3 or greater were regarded as significant fibrosis. Hyaluronic acid levels were measured using an enzyme-linked binding protein assay (2002 Corgenix, Inc) (adult reference range, 0-75 ng/mL; pediatric reference range, 0-30 ng/mL).
Twenty-three (25%) of 93 biopsies had significant fibrosis, and HA levels in this group were significantly higher than those with mild fibrosis (Ishak score, <3), (median level, 72 ng/mL vs 30 ng/mL; Mann-Whitney U test; P < 0.005). Hyaluronic acid level of 50 ng/mL had a positive predictive value 40% and negative predictive value 86% for significant fibrosis. An HA level 200 ng/mL has a sensitivity of 26% and specificity of 90%.
Hyaluronic Acid is a valid noninvasive predictor of hepatic fibrosis in unselected children with liver disease. An HA level of 200 ng/mL strongly suggests significant fibrosis. Hyaluronic acid level of less than 50 ng/mL accurately identifies those who do not have significant fibrosis.
透明质酸(HA)通过肝窦细胞粘附分子被肝脏清除。在肝纤维化时这种清除过程受到阻碍,导致血清HA水平升高。作为肝纤维化的一种非侵入性标志物,HA可能无需进行肝活检。
在未经过挑选的接受肝活检的儿童中评估HA作为肝纤维化标志物的情况。
前瞻性纳入了2003年4月至2004年3月期间连续93例未经过挑选的接受肝活检的儿童(中位年龄7.5岁;范围0.07 - 19岁)。同时进行肝活检和空腹HA水平检测。采用Ishak评分对纤维化进行分期。评分3分及以上被视为显著纤维化。使用酶联结合蛋白测定法(2002年,Corgenix公司)测量HA水平(成人参考范围0 - 75 ng/mL;儿童参考范围0 - 30 ng/mL)。
93例活检中有23例(25%)存在显著纤维化,该组的HA水平显著高于轻度纤维化组(Ishak评分<3)(中位水平分别为72 ng/mL和30 ng/mL;Mann - Whitney U检验;P < 0.005)。HA水平为50 ng/mL时,对显著纤维化的阳性预测值为40%,阴性预测值为86%。HA水平200 ng/mL时,敏感性为26%,特异性为90%。
透明质酸是未经过挑选的肝病儿童肝纤维化的有效非侵入性预测指标。HA水平200 ng/mL强烈提示存在显著纤维化。HA水平低于50 ng/mL可准确识别无显著纤维化的患儿。